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. 2023 Mar 6;48(8):1184–1193. doi: 10.1038/s41386-023-01553-z

Table 3.

Linear mixed effects models results comparing N-acetylcysteine to placebo on primary and secondary brain metabolite levels in the dorsal anterior cingulate cortex of adolescents who drink heavily.

Metabolite Fixed effect Estimate Std. error DF T-value p value η2p (95% CI)
Glx
Medication −0.03 0.23 29.31 −0.14 0.89 <0.01 (0.00–0.09)
Sequence 0.09 0.37 25.45 0.24 0.81
Visit 0.10 0.12 30.39 0.85 0.40
Baseline Glx 0.07 0.08 25.49 0.79 0.44
GM:BM −2.81 4.68 27.66 −0.60 0.55
Cannabis use days −0.18 0.30 36.47 −0.58 0.57
AUD 0.33 0.35 25.44 0.95 0.35
GABA+a
Medication 0.01 0.11 54.00 0.07 0.94 <0.01 (0.00–0.03)
Sequence 0.04 0.11 54.00 0.34 0.74
Visit −0.06 0.05 54.00 −1.16 0.25
Baseline GABA+ 0.11 0.13 54.00 0.86 0.39
GM:BM −2.39 1.67 54.00 −1.43 0.16
Cannabis use days −0.01 0.12 54.00 −0.07 0.95
AUD severity −0.07 0.06 54.00 −1.26 0.21
GSH
Medication 0.07 0.08 25.20 0.84 0.41 0.03 (0.00–0.24)
Sequence −0.06 0.14 22.91 −0.43 0.67
Visit 0.05 0.04 27.18 1.26 0.22
Baseline GSH 0.08 0.19 23.18 0.42 0.68
GM:BM −1.17 1.99 26.14 −0.59 0.56
Cannabis use days 0.02 0.14 45.91 0.11 0.91
Binge drinking episodes 0.07 0.04 47.99 1.81 0.08
Glu
Medication −0.13 0.16 28.11 −0.82 0.42 0.02 (0.00–0.22)
Sequence −0.00 0.25 24.97 0.01 0.99
Visit 0.04 0.08 29.67 0.52 0.61
Baseline Glu 0.10 0.08 25.19 1.28 0.21
GM:BM −4.20 3.33 27.48 −1.26 0.22
Cannabis use days 0.09 0.22 39.64 0.40 0.69
Binge drinking episodes −0.11 0.06 46.72 −1.76 0.08
tNAA
Medication −0.10 0.10 29.38 −1.02 0.31 0.03 (0.00–0.23)
Sequence −0.22 0.16 25.64 −1.34 0.19
Visit −0.04 0.05 30.63 −0.87 0.39
Baseline tNAA 0.62 0.11 25.61 5.60 <0.001
GM:BM −1.09 2.32 28.36 −0.47 0.64
Cannabis use days 0.13 0.15 29.29 0.90 0.37
AUD −0.34 0.17 25.57 −1.99 0.06
tCho
Medication −0.03 0.03 29.36 −0.91 0.37 0.03 (0.00–0.21)
Sequence −0.03 0.04 25.60 −0.68 0.50
Visit 0.01 0.01 30.49 0.81 0.42
Baseline tCho 0.98 0.11 26.20 9.16 <0.001
GM:BM −1.92 0.60 27.97 −3.18 0.004
Cannabis use days −0.04 0.04 28.06 −0.90 0.37
AUD −0.08 0.04 25.51 −1.83 0.08
tCr
Medication 0.08 0.08 29.48 0.94 0.35 0.03 (0.00–0.22)
Sequence −0.14 0.16 26.81 −0.87 0.39
Visit 0.00 0.04 30.41 0.04 0.97
Baseline tCr 0.59 0.15 27.13 3.93 <0.001
GM:BM −3.05 2.33 31.90 −1.31 0.20
Cannabis use days 0.07 0.14 47.79 0.49 0.62
Drinks per drinking day −0.04 0.03 50.29 −1.73 0.09
mI
Medication −0.07 0.11 29.42 −0.59 0.56 0.01 (0.00–0.18)
Sequence −0.18 0.19 26.42 −0.97 0.34
Visit −0.04 0.06 30.12 −0.78 0.44
Baseline mI 0.51 0.14 26.56 3.58 0.001
GM:BM −0.64 2.64 30.20 −0.24 0.81
Cannabis use days 0.01 0.17 42.69 0.06 0.95
Drinks per drinking day −0.02 0.03 53.26 −0.68 0.50

n = 31 for glutamate + glutamine (Glx), GABA+, and other secondary metabolites; n = 28 for glutathione (GSH). References: medication = placebo; sequence = placebo/N-acetylcysteine; visit = visit 4 (last MRI visit).

Glu glutamate, tNAA total N-acetylaspartate, tCho total choline-containing metabolites, tCr total creatine-containing metabolites, mI myo-inositol, AUD alcohol use disorder, GM:BM brain tissue composition [GM/(GM + WM)], η2p partial eta squared (reported only for medication).

Bold values indicate statistical significance.

aRandom intercepts were not appropriate for this model, resulting in higher degrees of freedom.